Our objective is to characterize specific aminergic and peptidergic neuronal systems in retinas of mammals including those of calf, rat and rabbit. We shall study biochemical and pharmacological properties, functions and modes of action; and shall attempt to determine whether specific subclasses of receptors mediate specific functions or regulatory mechanisms. Also, the relationship of one transmitter to another will be studied by determining whether the two transmitters can regulate a single adenylate cyclase system and whether one transmitter is involved in the release of another. Particular attention will be given to two dopamine receptor subtypes that we have demonstrated to be present in retina: D1 receptors mediating dopamine stimulation of adenylate cyclase and modulated by guanine nucleotide, and D2 receptors readily assessed by agonist and antagonist radioligand binding and regulated by both sodium ion and guanine nucleotide. The properties and functions of Alpha2-noradrenergic receptor sites, also sensitive to sodium ion, and serotonin agonist binding sites will be investigated as well. Certain of these aminergic receptor systems may mediate inhibition of adenylate cyclase, and sodium ion may be involved in this effect. Adenylate cyclase reconstitution experiments involving membrane-membrane fusion will be performed to explore adenylate cyclase mechanisms. In studies of neuropeptides primary emphasis will be given to the vasoactive intestinal peptide (VIP) system including VIP-stimulated adenylate cyclase and effects of VIP on other retinal transmitter systems. Regulation of glycogenolysis and tyrosine hydroxylase activity by VIP, other transmitters and cyclic AMP will also be investigated levels and release of VIP and somatostatin will be measured by immunoassay procedures. Release of amine and amino acid transmitters will be studied following uptake of labelled transmitter precursor in vitro. These experiments should help elucidate mechanism of transmitter-receptor adenylate cyclase and related interactions in retina and provide a basis for understanding these interactions in other areas of the CNS as well.